Supplements for Testosterone & Cortisol Balance

The trans-isomer of clomiphene — a selective estrogen receptor modulator (SERM) used off-label/investigationally as a 'fertility-sparing' testosterone therapy. By blocking estrogen feedback at the hypothalamus it raises LH, FSH, and endogenous testosterone while preserving sperm production, unlike exogenous testosterone, which suppresses both. Honest appraisal: Phase-2/3 RCTs show it raises testosterone and keeps sperm counts in the normal range vs topical testosterone — but it is NOT FDA-approved (Androxal failed to gain approval) and is compounded/off-label, and there are NO long-term hard-outcome trials (cardiovascular, bone, mortality).

The primary male androgen and an FDA-approved prescription drug for diagnosed male hypogonadism — and a Schedule III CONTROLLED SUBSTANCE. For men with genuinely low testosterone, randomized trials show real benefits: the Testosterone Trials (TTrials) improved sexual function, mood, anemia and bone density in older hypogonadal men, and the large TRAVERSE trial found TRT non-inferior to placebo for major cardiac events. But those benefits were modest and indication-specific, NOT a longevity or anti-aging result. It is prescription-only; non-medical, supraphysiologic, and 'anti-aging' use is illegal and carries serious harms — erythrocytosis, suppressed sperm production/fertility, cardiovascular and psychiatric risk. This is a harm-reduction reference, not a recommendation, and testosterone is NOT a dietary supplement.

A racemic selective estrogen receptor modulator (SERM) that has been FDA-approved for decades for female ovulation induction, and is used off-label in men with secondary (low-LH) hypogonadism to raise endogenous testosterone while preserving fertility. By blocking estrogen feedback at the hypothalamus it increases LH and FSH, driving the testes to make more testosterone — unlike testosterone gels/injections, which suppress both. Honest appraisal: clomiphene is the RACEMIC mixture of enclomiphene (trans, the active estrogen-antagonist isomer) and zuclomiphene (cis, a long-lived weakly estrogenic isomer that accumulates) — the zuclomiphene downside is the entire reason the single-isomer enclomiphene was developed. Male use is off-label, the evidence is mostly observational and surrogate-based (testosterone/LH/FSH), and there are NO long-term hard-outcome trials. It is NOT a longevity drug.

A non-steroidal aromatase inhibitor (Arimidex) approved for hormone-receptor-positive breast cancer, where its evidence is strong (ATAC). Used off-label in men to block the testosterone-to-estradiol conversion — it reliably raises testosterone and lowers estradiol, which is why it's reached for in TRT and in obese hypogonadal men. The honest catch: estrogen is required for the male skeleton, so estrogen suppression lowers bone-mineral density and raises fracture risk, and the male-hypogonadism trials normalized hormones without improving strength or body composition. A prescription drug, not a supplement, and NOT a longevity drug.

A steroidal, irreversible ('suicide') aromatase inhibitor (Aromasin) approved for hormone-receptor-positive breast cancer, where its evidence is strong (the IES switch trial, MAP.3 prevention, and head-to-head with anastrozole in MA.27). It is the steroidal counterpart to anastrozole and letrozole, and because its metabolite is mildly androgenic it is sometimes claimed to spare bone — but the trials show it still lowers bone-mineral density and raises fracture risk. Used off-label in men to lower estradiol and raise testosterone, a small crossover RCT confirms it does shift the hormones, but estrogen is required for the male skeleton and lipids. A prescription drug, not a supplement, and NOT a longevity drug.

An oral DHT-derived androgen (Proviron) — chemically 1α-methyl-dihydrotestosterone, non-aromatizable, that binds the androgen receptor weakly but binds sex-hormone-binding globulin (SHBG) very avidly. Marketed for male hypogonadism and idiopathic male infertility, and used off-label in bodybuilding for libido, 'hardening', and to free up bound testosterone by occupying SHBG. Honest appraisal: the fertility/infertility evidence is WEAK and largely NEGATIVE — a WHO multicentre RCT, a Belgian placebo-controlled trial, and a Cochrane review all FAILED to show a real pregnancy or sperm benefit over placebo — and it is a prescription androgen (an anabolic-androgenic steroid), not a dietary supplement, with DHT-mediated hair-loss/prostate and lipid concerns.